Pilot Study of Mycophenolate Mofetil in Congenital Uropathies

NCT00193635 | Completed Phase 1 DMC

• 1 other identifier: CEL214
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 3

Brief Summary

Congenital or hereditary structural anomalies of the genitourinary tract account for approximately half of all cases of end stage renal disease in the pediatric population. Despite optimal medical management, when the GFR falls below 50 ml/min/1.73 M2, nearly 40% of affected children will require dialysis or a renal transplant within 2 years. At present, there is no specific treatment for patients with congenital uropathies that can retard the progressive loss of kidney function and forestall the need for renal replacement therapy. There is evidence in experimental animals and in patients with chronic renal failure (CRF) that immunoeffector mechanisms are activated within the renal parenchyma. Infiltration of the kidney by macrophages, monocytes, and lymphocytes, activation of renal tubular epithelial cells, and release of pro-inflammatory cytokines result in fibrosis and irreversible organ damage. Mycophenolate mofetil (MMF) is a new immunosuppressive agent that is used to prevent acute rejection in kidney transplant recipients. It attenuates renal damage in the remnant kidney model of CRF in which there is no primary immunological injury. Therefore, this pilot study is designed to test the hypothesis that immunosuppressive treatment with MMF in children with structural causes of CRF will be safely tolerated and that this therapy will retard progressive decline in renal function. Patients with congenital uropathy, 3-16 years of age and with a GFR less than 50 ml/ml/1.73 M2, will be treated with MMF for 24 months. The two primary endpoints are: (1) safety and tolerance of the drug; and (2) need for dialysis or kidney transplantation. It is anticipated that the MMF will be free of significant toxicity and that administration of the drug will reduce the frequency of progression to end stage renal disease from 38% to 19%. Patients will be followed at 3-month intervals and they will undergo serial assessment of proteinuria, estimated GFR and iothalamate clearance, urinary cytokine excretion, urine flow cytometry, and immunologic testing. The significance of this pilot study is that it may provide evidence in support of a randomized, double-blind, placebo-controlled trial of immunological treatment of congenital structural causes of CRF in children

Conditions

Congenital Urological Abnormalities

Keywords

Congenital uropathies; Mycophenolate mofetil; GFR; Iothalamate clearance; Urine cytometry; Children; Congenital urological abnormalities which represent stuctural defects in the genitourinary system

Outcome Measures

Primary Outcomes (1)

• Reduction in GFR

  24 month treatment period

Secondary Outcomes (1)

• Safety and tolerance of MMF

  24 month treatment period

Study Arms (1)

1

ACTIVE COMPARATOR

oral MMF

Drug: mycophenolate mofetil

Interventions

mycophenolate mofetil DRUG

oral drug administration

Also known as: Cellcept

1

Eligibility Criteria

• Age: 3 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 3-16 GFR \<50 ml/min/1.73 m2 Congenital abnormality of urinary tract

You may not qualify if:

• Known hepatic, hematologic, GII, infectious disease Sensitivity to MMF Glomerular disease

Sponsors & Collaborators

• Northwell Health: lead
• Hoffmann-La Roche: collaborator
• University of Medicine and Dentistry of New Jersey: collaborator
• New York Presbyterian Hospital: collaborator

Study Sites (3)

Robert Wood Johnson Medical center

New Brunswick, New Jersey, 08903-0019, United States

Location

Schneider Children's Hospital

New Hyde Park, New York, 11040, United States

Location

Cornell Weill Medical Center

New York, New York, 10021-4873, United States

Location

Related Publications (1)

• Trachtman H, Christen E, Frank R, Rini J, Palestro C, Perelstein E, Weiss L, Tarapore F, Fortune S, Horowitz J. Pilot study of mycophenolate mofetil for treatment of kidney disease due to congenital urinary tract disorders in children. Am J Kidney Dis. 2008 Oct;52(4):706-15. doi: 10.1053/j.ajkd.2008.03.035. Epub 2008 Jun 13.

  PMID: 18554762 DERIVED

MeSH Terms

Interventions

Mycophenolic Acid

Intervention Hierarchy (Ancestors)

Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids

Study Officials

• Howard Trachtman, MD

  Schneider Children's Hospital of North Shore-LIJ Health System

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 9, 2005
• First Posted: September 19, 2005
• Study Start: March 1, 2002
• Study Completion: August 1, 2007
• Last Updated: October 19, 2007

Record last verified: 2007-10

Locations

US (3)